Incretin and Cardiovascular Effects of Weight Loss and Remission of Prediabetes

Since the incretins GLP-1 and GIP have important roles in insulin sensitivity and have been shown to be effective in pharmacological treatment of type 2 Diabetes, we studied these incretin level changes with weight loss and remission of prediabetes in 24 obese women and men with prediabetes. Our studies have shown that prediabetes subjects on a 6 month HP diet (30% protein, 30% fat, 40% CHO) had 100% remission of prediabetes compared to only 33% on a HC diet (15% protein, 30%fat, 55% CHO). Subjects on the HP diet had increased satiety compared to the HC diet, therefore, we studied HP and HC diet effects on ghrelin levels. Additionally, since cardiovascular risk factors (CVRF) decreased more in the HP than the HC diet, we determined if the B-Type Natriuretic Peptide(BNP) released from the heart was affected by either diet. GLP-1, GIP, Ghrelin, and BNP levels were determined with a Meal Tolerance Test (MTT) at baseline and after 6 mo on HP and HC diets where all food was provided. The active GLP-1 and total GIP area under the curves for the HP MTT increased significantly from baseline vs. 6 months (7860±31 vs. 8970±37 pmol/l/min, p=0.001) and (21,350±63 vs. 27,240±72 pg/ml/min, p=0.001) respectively. The ghrelin decreased significantly from baseline vs. 6 months on the HP MTT (338±21 vs. 78±14 pg/ml/min, p= 0.005). BNP decreased significantly from baseline (126±11pmol/l) to 6 months (78±9 pmol/l), p=0.01. HP diet had a significantly greater increase in GLP-1 and GIP than the HC diet. HP ghrelin results demonstrate that HP diet can induce satiety and is more effective than the HC diet. The BNP decrease in both groups demonstrates the improvement in heart tissue with the HP diet having a greater effect than the HC diet. Although weight loss was similar (9.8% in HP vs. 11.3% in HC, p=0.692), this study demonstrates that the HP diet increases GLP-1 and GIP which may be responsible in part for the improved insulin sensitivity, and decreases BNP with greater improvement in CVRF with remission of prediabetes. Disclosure F.B. Stentz: None. A. Ammons: None.